Regulatory role of galanin in control of hypothalamic-anterior pituitary function.

Regulatory role of galanin in control of hypothalamic-anterior pituitary function.
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甘丙肽在控制下丘脑垂体前叶功能中的调节作用。

DOI:
10.1073/pnas.85.24.9861
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发表时间:
1988
影响因子:
11.1
通讯作者:
McCann,SM
McCann,SM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ottlecz,A;Snyder,GD;McCann,SM

文献摘要

被引文献

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在清醒雄性大鼠体内和体外培养的垂体前叶细胞中研究了神经肽甘丙肽在垂体前叶功能调节中的作用。将甘丙肽(50-200 ng; 15-60 pmol)注射到大鼠第三脑室中,可使血浆生长激素(GH)浓度产生高度显著的剂量相关性增加,而甘丙肽仅在最高剂量(60 pmol)下可增加催乳素(PRL)并降低促甲状腺激素(TSH)水平。静脉注射甘丙肽不能改变这些大鼠的PRL和TSH水平。与脑室内注射肽的结果相反,静脉注射30或300 pmol甘丙肽产生小的,短暂的,剂量相关的血浆GH增加。对300 pmol剂量的反应小于由低20倍的脑室内剂量引起的反应,这建立了甘丙肽的中枢作用。甘丙肽的浓度范围从1 nM到1 μ M未能改变显着的GH,PRL,或TSH从分散的垂体前叶细胞的释放。它也未能改变响应于100 nM GH释放激素的GH分泌;然而,在该剂量下,甘丙肽确实增强了100 nM TSH释放激素对TSH和PRL释放的影响。因此,第三脑室注射肽的作用是由下丘脑介导的。为了确定甘丙肽在控制垂体激素释放中的生理意义,脑室注射高度特异性的抗甘丙肽的抗血清。第三脑室注射3微升甘丙肽抗血清导致血浆GH值在15分钟内与注射正常兔血清的对照组相比急剧下降,这种情况一直持续到实验结束(注射后5小时)。甘丙肽抗血清并没有降低血浆PRL或TSH水平在任何时间段后,其第三脑室注射,然而,血浆TSH水平的短暂增加发生在30和60分钟后,与正常兔血清注射对照组的TSH水平相比。由于抗血清对血浆PRL没有影响,而TSH只是短暂升高,甘丙肽在静息状态下可能没有足够的生理意义来改变雄性大鼠的PRL和TSH释放。甘丙肽抗血清的实验结果表明,内源性甘丙肽在下丘脑内具有刺激GH释放的滋补作用。甘丙肽和针对它的抗血清的作用的快速发作表明,它的作用是刺激从脑室周围结构释放GH释放激素,然后刺激GH的释放。
The role of the neuropeptide galanin in the regulation of anterior pituitary function was studied in vivo in conscious male rats and in vitro with cultured anterior pituitary cells. Galanin (50-200 ng; 15-60 pmol) injected into the third cerebral ventricle of rats produced highly significant, dose-related increases of plasma growth hormone (GH) concentrations, whereas galanin increased prolactin (PRL) and decreased thyroid-stimulating hormone (TSH) levels only at the highest dose (60 pmol) tested. Intravenous galanin failed to alter PRL and TSH levels in these rats. In contrast with the results with intraventricular injection of the peptide, intravenous injection of 30 or 300 pmol of galanin produced small, brief, dose-related increases in plasma GH. The response to the 300-pmol dose was less than that induced by a factor-of-20-lower intraventricular dose, which establishes a central action of galanin. Galanin in concentrations ranging from 1 nM to 1 microM failed to alter significantly GH, PRL, or TSH release from dispersed anterior pituitary cells. It also failed to alter GH secretion in response to 100 nM GH-releasing hormone; however, at this dose galanin did potentiate the effect of 100 nM TSH-releasing hormone on TSH and PRL release. Thus, the effects of third-ventricular injection of the peptide are mediated by the hypothalamus. To determine the physiological significance of galanin in control of pituitary hormone release, highly specific antiserum against galanin was injected intraventricularly. Third-ventricular injection of 3 microliter of galanin antiserum resulted in a dramatic decrease in plasma GH values as compared with those of normal rabbit serum-injected controls within 15 min, which persisted until the end of the experiment (5 hr postinjection). Galanin antiserum did not decrease plasma PRL or TSH levels at any time period after its third-ventricular injection; however, a transient increase of plasma TSH levels occurred after 30 and 60 min in comparison with TSH levels in normal rabbit serum-injected controls. Since there was no effect of the antiserum on plasma PRL and only a transient elevation in TSH, galanin may not be physiologically significant enough during resting conditions to alter PRL and TSH release in the male rat. The results of the experiments with galanin antiserum indicate that endogenous galanin has a tonic action within the hypothalamus to stimulate GH release. The rapidity of onset of the effects of galanin and the antiserum directed against it suggest that it acts to stimulate release of GH-releasing hormone from periventricular structures, which then stimulates the release of GH.